Plantibodies: A New Approach for Immunomodulation in Human Health
Introduction
Antibodies or immunoglobulins are the vital component of
adaptive immune system in mammals. These are mainly present
in the body fluid and constitute an assembly of glycoproteins
released by B-cells. B-cells constitute the humoral type of
adaptive immune system. They are highly specific their mode of
action. First they recognize their target specifically, binds to the
antigen/toxin of pathogen and produce and elicit the immune
response. These features permit immunoglobulins to be employed
in diverse range of applications such as diagnosis, prevention
and treatment [1]. Production of defective antibody response
results in increased vulnerability to pyogenic infections due to
impairment in B-cell function, e.g. in hyper-IgM syndrome as a
result of improper signaling between B and T cells and in X-linked
agammaglobulinemia. To overcome these defects, constant region
of a human immunoglobulin is modified by transgenic approach
to create recombinant antibody [2]. With this advancement, a new
expectation of a reliable, inexpensive cure for diseases like, diabetes
and cancer was awakening; but the major drawback was its cost
ineffectiveness.
Hence, production of cost-effective and scalable platforms
that is safe for therapeutics is urgently required [3]. Transgenics
is one of the most potential applications in therapeutics for the
preparation of various biological substances such as antibodies,
proteins and vaccines. They can be produced from plants by
transforming antibody-coding genes from humans to plants as
‘transgene’. Plants acts as suitable host for production of antibodies
referred as “plantibodies”. The term “plantibodies” describes
plant based products which contained antibody and its fragments;
produced by genetically engineering. Hence, plants are largely used
as a host or bioreactors by exploiting their endomembrane and
secretory system to generate huge amount of biological proteins of
clinical importance (either full-length or smaller length fragments).
This opens a new era in plant biology research. A wide variety of
plants functionally expressed different types of recombinant by
exploiting the same pathway for the assembly of heavy chain and
light chain signal peptides followed by proper folding and assembly
as in mammalian cells [4].
Benefits of Using Plants as Host For Mammalian Antibody Production
Plantibodies functions in a similar way to mammalian
antibodies. It offers numerous unique advantages over conventional
methods. Firstly, plants are less prone to mammalian pathogens; this
property reduces screening costs for bacterial toxins, prions and
viruses. Both plants and humans have a similar endomembrane and
secretory pathway system. Secondly, plants are widely distributed;
their maturation time completes in a short period of time, say for
example, in one season; which enables their production in a short
period of time. Hence they are the cost-effective compared to their
animal counterparts [5]. Exposure to mammalian antibodies do
not trigger plants immune response compared as compared to
mammalian system. Production of large amount of antibodies,
comparatively in short time period is the most fascinating benefit
of plants as host [6]. Comparatively, crops, for example, corn and
tobacco which have higher biomass may act as good candidate in
genetic engineering process; where biological products and viable
proteins (stored in seed for an indefinite period) will be produced
in large amounts with small decline in their catalytic activity [5].
Plants viz. corn, tobacco, soybean and other crops shows
potential alternative for production of therapeutic proteins. Crops
having maximum biomass/hectare such as alfalfa and tobacco may
be a best alternative for antibodies production. Tobacco, a non-feed
crop proves to be the most potential crop for large scale production
of therapeutic antibodies. In transgenic tobacco, antibodies against
melanoma, human papillomavirus, B-cell lymphoma, colon,
testicular have been produced. These tobacco based plantibodies
are still under progress for commercial use in human health.
Uses of Plantibodies in Medicine
Genetically engineered plants/transgenic plants used as host
for plantibodies production represents a huge prospect for the
pharmaceuticals. Among all the pharmaceutical compounds,
maximum contribution is accompanied by recombinant proteins.
Presently, clinical trials are going on a number of plantibodies
for their therapeutic role. In therapeutics, CaroRx® was the first
plantibody produced from tobacco. It is anti-Streptococcus mutans
secretory antibody and protects from dental caries. Another
plantibody was developed in soybean against herpes simplex
virus [7]. USDA has approved CaroRx®, a plantibody for humans;
expressed in tobacco, against poultry virus [8]. Plants expressing
clinical proteins and polypeptides of pharmaceutical importance
such as human C protein, interferons, hormones, and cytokines
are currently used to provide immunization for example, oral
immunization. Edible vaccines expressed in edible tissue of plants
have proved to be an excellent source for expression of desirable
antigens and their fragments. This is a cost effective method to
provide immunization via. oral mean. Combining these, genetically
engineered plants proved to be superior system for vaccination in
humans. Recently, antibodies against Ebola virus infection has been
explored in tobacco (Nicotiana benthamiana).
Conclusion
Genetically engineered plants acts as most desirable and
promising host for expression of plantibodies for humans. They
stably express antibodies and its fragments and edible vaccines
in their edible tissues which are of therapeutic importance. Highscalability,
low-cost and safety characteristics present an attractive
approach for commercialization of pharmaceutical products for the
developing world.
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